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Y132G
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10% increase in catalytic efficiency
Y132G/V309K
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loss of activity
Y132G/V309W
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loss of activity
R63K
mutant is able to use NADH as cofactor
R63K/R64H
increases enzymatic activity by 13.8fold with NADH as cofactor
R64G
mutant exhibits significantly improved activity with NADH
R64H
mutant exhibits significantly improved activity with NADH
R64S
mutant exhibits significantly improved activity with NADH
R64T
mutant exhibits significantly improved activity with NADH
C352G
-
site-directed mutagenesis, mutation at the substrate binding site, the mutant shows reduced activity compared to the wild-type enzyme
D181T/L182Q
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site-directed mutagenesis, mutation at motif V, the mutant shows reduced activity compared to the wild-type enzyme
F353M
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site-directed mutagenesis, mutation at the substrate binding site, the mutant shows similar activity as the wild-type enzyme
F353P
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site-directed mutagenesis, mutation at the substrate binding site, the mutant shows similar activity as the wild-type enzyme
G204N
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site-directed mutagenesis, mutation at motif IV, the mutant shows reduced activity compared to the wild-type enzyme
L182Q
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site-directed mutagenesis, mutation at motif V, the mutant shows similar activity as the wild-type enzyme
M150L
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site-directed mutagenesis, mutation at motif IV, the mutant shows similar activity as the wild-type enzyme
N205A
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site-directed mutagenesis, mutation at the substrate binding site, the mutant shows increased activity compared to the wild-type enzyme
N205M
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site-directed mutagenesis, mutation at the substrate binding site, the mutant shows increased activity compared to the wild-type enzyme
N205M/Y156V
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site-directed mutagenesis, double mutation at the substrate binding site, the mutant shows increased activity compared to the wild-type enzyme
R146T
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site-directed mutagenesis, mutation at motif IV, the mutant shows similar activity as the wild-type enzyme
S248M
-
site-directed mutagenesis, mutation near the substrate binding site, inactive mutant
T65P
-
site-directed mutagenesis, mutation at near motif II, the mutant shows similar activity as the wild-type enzyme
Y156V
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site-directed mutagenesis, mutation at the substrate binding site, the mutant shows increased activity compared to the wild-type enzyme
Y302F
-
site-directed mutagenesis, mutation at motif IV, the mutant shows similar activity as the wild-type enzyme
E120A
-
mutant is devoid of activity
R217stop
the naturally occuring mutation of gene SRD5B1 are involved in hyper-3-oxo-DELTA4 bile aciduria from primary 3-oxo-DELTA4-steroid 5beta-reductase deficiency, phenotypes, overview
V309F
replacement of one of the residues delineating this site by a phenylalanine completely abolishes the enzyme's substrate inhibition, but the catalytic efficiency of the mutated enzyme is similar to that of the wild-type h5beta-red enzyme
Y132F
replacement of one of the residues delineating this site by a phenylalanine completely abolishes the enzyme's substrate inhibition, but the catalytic efficiency of the mutated enzyme is similar to that of the wild-type h5beta-red enzyme
Y58F
-
mutant is devoid of activity
G223E
the naturally occuring mutation of gene SRD5B1 are involved in hyper-3-oxo-DELTA4 bile aciduria from primary 3-oxo-DELTA4-steroid 5beta-reductase deficiency, phenotypes, overview
G223E
-
naturally occuring mutation, identified in patients with functional bile acid deficiency, a non-synonymous point mutations in highly conserved portions of the AKR1D1 gene
G223E
naturally occuring mutation, identified in patients with functional bile acid deficiency, inactive mutant
L106F
mutant identified in patient with reduced enzymic activity
L106F
-
naturally occuring mutation, identified in patients with functional bile acid deficiency, a non-synonymous point mutations in highly conserved portions of the AKR1D1 gene
L106F
naturally occuring mutation, identified in patients with functional bile acid deficiency, almost inactive mutant
P133R
mutant identified in patient with reduced enzymic activity
P133R
mutant identified in patient with reduced enzymic activity. Mutant displays a highly reduced Km and Vmax reminiscent of uncompetitive kinetics with 4-cholesten-7alpha-ol-3-one as substrate. Mutant displays no change in cofactor affinity but is more thermolabile in the absence of NADPH
P133R
-
naturally occuring mutation, identified in patients with functional bile acid deficiency, a non-synonymous point mutations in highly conserved portions of the AKR1D1 gene. The mutant exhibits reduced Km and kcat with the bile acid intermediate DELTA4-cholesten-7alpha-ol-3-one as substrate reminiscent of uncompetitive inhibition
P133R
naturally occuring mutation, identified in patients with functional bile acid deficiency, AKR1D1-P133R activity is significantly reduced compared with wild-type enzyme
P198L
662C -T missense mutation in AKR1D1 causing an almost total absence of 5beta-reduced metabolites of corticosteroids and severely reduced production of 5beta-reduced metabolites of other steroids leading to hepatic failure of the homozygous mutant person, phenotype, overview. Heterozygous persons for the mutation show no phenotype or attenuated 5beta-reduction of cortisol, serum bile acid contents of mutant persons, overview
P198L
mutant identified in patient with reduced enzymic activity
P198L
-
naturally occuring mutation, identified in patients with functional bile acid deficiency, a non-synonymous point mutations in highly conserved portions of the AKR1D1 gene
P198L
naturally occuring mutation, identified in patients with functional bile acid deficiency, inactive mutant
R261C
mutant identified in patient with reduced enzymic activity
R261C
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naturally occuring mutation, identified in patients with functional bile acid deficiency, a non-synonymous point mutations in highly conserved portions of the AKR1D1 gene
R261C
naturally occuring mutation, identified in patients with functional bile acid deficiency, almost inactive mutant
additional information
determination of AKR1D1 reaction mechanism by mutational analysis revealing that the 4-pro-R hydride is transferred from the re-face of the nicotinamide ring to C5 of the steroid substrate. E120, a unique substitution in the AKR catalytic tetrad, permits a deeper penetration of the steroid substrate into the active site to promote optimal reactant positioning. It participates with Y58 to create a superacidic oxyanion hole for polarization of the C3 ketone, no role for K87 in the proton relay, overview
additional information
-
determination of AKR1D1 reaction mechanism by mutational analysis revealing that the 4-pro-R hydride is transferred from the re-face of the nicotinamide ring to C5 of the steroid substrate. E120, a unique substitution in the AKR catalytic tetrad, permits a deeper penetration of the steroid substrate into the active site to promote optimal reactant positioning. It participates with Y58 to create a superacidic oxyanion hole for polarization of the C3 ketone, no role for K87 in the proton relay, overview